A. Field of the Invention
This invention relates to compositions useful for inducing immunoprotection against infections by pathogenic organisms containing phosphocholine antigens, including Streptococcus pneumoniae and other microorganisms that have a phosphocholine antigen component in their capsules or membranes. This invention also relates to vaccines and methods for inducing immunoprotection against infection by these pathogenic organisms.
B. Background
Phosphocholine is an antigenic component in a variety of pathogenic organisms. These include a variety of bacteria which contain phosphocholine as a component of the bacterial cell wall. Examples of such bacteria include Streptococcus group O +H bacteria, Streptococcus pneumoniae, various species of Pseudomonas and Proteus Morganii, and Lactobacillus acidophilus. Fungi include Trichoderma, Fusarium and Aspergillus. In addition, there are a variety of parasites, including parasitic nematode worms such as Ascaris and Nippostrongeloides which have phosphocholine antigens.
Streptococcus pneumoniae remains an important pathogenic bacterium even with anti-microbial therapies available for its treatment. It is a commensal, normally non-pathogenic bacterium found in many individuals from infancy through adulthood, but as an opportunistic pathogen is responsible for several diseases. Three of these diseases, bacteremia, pneumonia and meningitis, are life threatening unless there is active intervention. Currently, the treatment most often prescribed involves the use of penicillin analogues or erythromycin, but recently an increasingly higher incidence of penicillin and multi-drug resistant strains have been isolated.
It is preferable to vaccinate against S. pneumoniae rather than treat the disease, both to reduce the incidence of pneumococcal diseases and to overcome the problem of the antibiotic resistant strains. An effective vaccine against S. pneumoniae should be given early in life, because infants may routinely suffer multiple episodes of S. pneumoniae infections by two years of age. Additionally, an ideal vaccine needs to be cross-reactive between all the various strains of S. pneumoniae. This is particularly relevant for S. pneumoniae since the pathogenic strains vary geographically.
The current pneumococcal vaccine is composed of the purified capsular polysaccharides from 23 of the 83 different strains of S. pneumoniae, including the strains most prevalent in specific pathological conditions in the United States. In normal adults, the current pneumococcal polysaccharide vaccine is 80% effective at preventing infection with S. pneumoniae, but it is much less effective in infants, and in senescent and immunocompromised patients. Unfortunately these groups represent some of the high risk populations most in need of the protection.
A type specific antibody response is achieved in non-infant recipients for most of the S. pneumoniae strains represented in the vaccine. However, some of the more important pathogenic strains do not induce antibody responses in children under five years of age. Repeat immunizations do not significantly improve this situation in children under the age of two years. There are also clear instances where vaccination has failed to produce protective antibodies to the homologous strain in this age group. This is primarily because infants lack the immunological maturity to produce anti-carbohydrate antibodies.
There is the additional problem that the vaccine is less effective in geographic areas where the common pathogenic strains are not included in the vaccine. Construction of the vaccine was based on the epidemiological studies of Europe and the United States, so this affects geographic areas primarily outside the United States and Europe. The failure of the current pneumococcal capsular vaccine to protect those individuals most at risk for infection with S. pneumoniae and the geographical limitations of the current vaccine indicate that a more comprehensive streptococcal vaccine capable of overcoming these problems is needed.
This invention relates to phosphocholine conjugates capable of protecting normal or immunocompromised animals, including humans, from infection from pathogenic organisms. Examples of such pathogenic organisms include S. pneumoniae and other bacteria having a phosphocholine (PC) component in their cell walls. These conjugates are haptens containing phosphocholine which are conjugated to carrier molecules or substances. The invention also relates to vaccines based on these phosphocholine conjugates and to methods of immunizing animals, including humans, to infection by S. pneumoniae and other pathogenic organisms having PC as a component of their cell membranes or capsids.